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dc.contributor.authorHaslene-Hox, Hanneen_US
dc.contributor.authorMadani, Aminaen_US
dc.contributor.authorBerg, Kaja Christine Graueen_US
dc.contributor.authorWoie, Kathrineen_US
dc.contributor.authorSalvesen, Helga Birgitteen_US
dc.contributor.authorWiig, Helgeen_US
dc.contributor.authorTenstad, Olaven_US
dc.date.accessioned2014-12-02T14:30:34Z
dc.date.available2014-12-02T14:30:34Z
dc.date.issued2014-12eng
dc.identifier.issn2214-6474
dc.identifier.urihttps://hdl.handle.net/1956/8807
dc.description.abstractBackground: Tumor interstitial fluid (TIF) rather than plasma should be used in cancer biomarker discovery because of the anticipated higher concentration of locally produced proteins in the tumor microenvironment. Nevertheless, the actual TIF-to-plasma gradient of tumor specific proteins has not been quantified. We present the proof-of-concept for the quantification of the postulated gradient between TIF and plasma. Methods: TIF was collected by centrifugation from serous (n = 19), endometrioid (n = 9) and clear cell (n = 3) ovarian carcinomas with early (n = 15) and late stage (n = 16) disease in grades 1 (n = 2), 2 (n = 8) and 3 (n = 17), and ELISA was used for the determination of CA-125, osteopontin and VEGF-A. Results: All three markers were significantly up-regulated in TIF compared with plasma (p b 0.0001). The TIF-toplasma ratio of the ovarian cancer biomarker CA-125 ranged from1.4 to 24,300 (median=194) andwas inversely correlated to stage (p = 0.0006). The cancer related osteopontin and VEGF-A had TIF-to-plasma ratios ranging from 1 to 62 (median = 15) and 2 to 1040 (median = 59), respectively. The ratios were not affected by tumor stage, indicative of more widespread protein expression. Conclusion: We present absolute quantitative data on the TIF-to-plasma gradient of selected proteins in the tumor microenvironment, and demonstrate a substantial and stage dependent gradient for CA-125 between TIF and plasma, suggesting a relation between total tumor burden and tissue-to-plasma gradient. General significance: We present novel quantitative data on biomarker concentration in the tumor microenvironment, and a new strategy for biomarker selection, applicable in future biomarker studies.en_US
dc.language.isoengeng
dc.publisherElseviereng
dc.relation.ispartof<a href="http://hdl.handle.net/1956/8809" target="blank">The microenvironment in human ovarian carcinoma - characterization through proteomic analysis of tissue interstitial fluid</a>eng
dc.rightsAttribution-NonCommercial-NoDerivs CC BY-NC-NDeng
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/eng
dc.subjectCA-125eng
dc.subjectBiomarkereng
dc.subjectOvarian carcinomaeng
dc.subjectTumor microenvironmenteng
dc.subjectTumor interstitial fluideng
dc.titleQuantification of the concentration gradient of biomarkers between ovarian carcinoma interstitial fluid and blooden_US
dc.typePeer reviewed
dc.typeJournal article
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2014 The Authors. Published by Elsevier B.V.
dc.identifier.doihttps://doi.org/10.1016/j.bbacli.2014.08.002
dc.identifier.cristin1159207
dc.source.journalBBA Clinical
dc.source.402
dc.source.pagenumber18-23


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